From the Guidelines
Transforming growth factor beta-induced (TGFBI) corneal dystrophies are a group of inherited disorders characterized by abnormal protein deposits in the cornea, leading to visual impairment, and management should prioritize conservative approaches and corneal transplantation, with phototherapeutic keratectomy (PTK) being a viable option for treating recurrences or superficial disease, as supported by the most recent study 1.
Presentation and Diagnosis
These dystrophies include Reis-Bücklers, Thiel-Behnke, lattice type 1, granular type 1, and granular type 2 (Avellino) dystrophies, all caused by mutations in the TGFBI gene on chromosome 5q31. The specific presentation varies by subtype:
- Reis-Bücklers presents with geographic opacities in the anterior cornea
- Thiel-Behnke shows honeycomb-shaped opacities
- Lattice dystrophy features linear amyloid deposits
- Granular dystrophy shows discrete, crumb-like deposits
- Avellino dystrophy displays a combination of granular and lattice features Symptoms typically appear in the first or second decade of life and include recurrent corneal erosions, pain, photophobia, and progressive visual impairment.
Management and Treatment
Management initially focuses on conservative approaches, including:
- Lubricating drops
- Bandage contact lenses
- Hypertonic saline for erosions As the disease progresses, corneal transplantation becomes necessary.
- Anterior lamellar keratoplasty is now preferred when the disease affects only the anterior cornea, preserving the patient's endothelium and reducing rejection risk, as indicated by the most recent study 1.
- Penetrating keratoplasty (full-thickness transplant) was traditionally used. Unfortunately, TGFBI dystrophies have high recurrence rates after transplantation, with deposits typically appearing within 2-5 years post-surgery.
- Phototherapeutic keratectomy (PTK) can be used to treat recurrences or as primary treatment for superficial disease, removing the abnormal deposits while preserving corneal tissue, as supported by the study 1.
Corneal Transplantation and Recurrence
Corneal transplantation, either full-thickness penetrating keratoplasty (PK) or as a lamellar procedure, is the most common therapeutic option chosen by patients who have corneal edema and reduced vision or significant pain due to bullous keratopathy.
- Factors that impact success after keratoplasty include lower preoperative visual acuity and visual functioning, younger age, and male gender, as reported in the study 1. Recurrence occurs because the host keratocytes that migrate into the donor tissue carry the genetic mutation.
- Regular follow-up is essential for early detection of recurrence, and patients should be counseled about the hereditary nature of these conditions, as they follow an autosomal dominant inheritance pattern with high penetrance, as indicated by the study 1.
From the Research
Presentation of TGFB1 Corneal Dystrophies
- The TGFB1 corneal dystrophies are a group of inherited disorders that affect the cornea, leading to visual impairment 2.
- They are characterized by the deposition of insoluble protein materials in the form of extracellular deposits or intracellular cysts 2.
- The severity, clinicopathogenic variations, age of onset, and location of the deposits depend on the type of amino acid alterations in the protein 2.
- Mutations in the TGFBI gene are responsible for superficial and stromal corneal dystrophies, including granular corneal dystrophy and lattice corneal dystrophy 3.
Recurrence of TGFB1 Corneal Dystrophies
- Recurrence of granular corneal dystrophy type 1 (GCD1) can occur after surgical interventions, including phototherapeutic keratectomy (PTK), lamellar keratoplasty, and penetrating keratoplasty (PKP) 4.
- The time required to achieve best-corrected visual acuity (BCVA) after each intervention varies, with PTK providing the fastest visual recovery but with shorter recurrence-free survival 4.
- Significant recurrence-free survival was longer for PKP than for other surgical interventions, including ALK, DALK, and PTK 4.
Corneal Transplants for TGFB1 Corneal Dystrophies
- Corneal transplants, including penetrating keratoplasty (PKP) and lamellar keratoplasty, can be used to treat TGFB1 corneal dystrophies 5, 4.
- Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases 5.
- Deep anterior lamellar keratoplasty (DALK) can be used to treat granular corneal dystrophy, and optical coherence tomography (OCT) can help determine the location of deposits and choose between surgical interventions 6.